Safety of dermatologic medications in pregnancy and lactation: An Update - Part II: Lactation.

Multiple recently approved medications have been added to our treatment armamentarium for various dermatologic conditions. Herein, we have reviewed the literature, consolidated available safety data, and offered recommendations based upon available evidence as a reference guide for clinicians treating patients for dermatologic conditions during lactation.

Dupilumab-induced psoriasiform dermatitis in two pediatric cardiac transplant patients.

Dupilumab is an interleukin-4 receptor antagonist important in the treatment of refractory atopic dermatitis (AD), particularly among pediatric patients. Two boys with a history of AD and cardiac transplant who developed psoriasiform dermatitis in response to dupilumab therapy are reported. These patients paradoxically developed an immune-mediated adverse drug reaction despite taking systemic immunosuppressive agents. While the literature suggests possible pathomechanisms for psoriasiform dermatitis despite immunosuppression, further research is necessary to better characterize this unique and unexpected phenomenon.

Silica-based microencapsulation used in topical dermatologic applications.

Microencapsulation has received extensive attention because of its various applications. Since its inception in the 1940s, this technology has been used across several areas, including the chemical, food, and pharmaceutical industries. Over-the-counter skin products often contain ingredients that readily and unevenly degrade upon contact with the skin. Enclosing these substances within a silica shell can enhance their stability and better regulate their delivery onto and into the skin. Silica microencapsulation uses silica as the matrix material into which ingredients can be embedded to form microcapsules. The FDA recognizes amorphous silica as a safe inorganic excipient and recently approved two new topical therapies for the treatment of rosacea and acne. The first approved formulation uses a novel silica-based controlled vehicle delivery technology to improve the stability of two active ingredients that are normally not able to be used in the same formulation due to potential instability and drug degradation. The formulation contains 3.0% benzoyl peroxide (BPO) and 0.1% tretinoin topical cream to treat acne vulgaris in adults and pediatric patients. The second formulation contains silica microencapsulated 5.0% BPO topical cream to treat inflammatory rosacea lesions in adults. Both formulations use the same amorphous silica sol-gel microencapsulation technology to improve formulation stability and skin compatibility parameters.

Efficacy of single dose dermatological 0.1% Tacrolimus Ointment in the treatment of vernal keratoconjunctivitis.

Objectives: To assess the safety of dermatological 0.1% tacrolimus ointment when used topically and its efficacy in the treatment of vernal keratoconvinctivtis. METHODS: The quasi-experimental, multi-centre study was conducted at the Gujranwala Medical College/District Headquarters Teaching Hospital, Gujranwala, and the Gomal Medial College/Mufti Mehmood Teaching Hospital, Dera Ismail Khan, Pakistan, from July 2019 to March 2020, and comprised patients of severe vernal keratoconvinctivtis. Symptoms and clinical signs were graded on a pre-devised scale. Patients were given small amount of tacrolimus 0.1% ointment applied to the inferior conjunctival fornix before going to bed. The duration of treatment was 3 months and the patients were followed up for up to 6 months. Data was analysed using SPSS 20. RESULTS: Of the 50 patients, 30(60%) were males and 20(40%) were females. The overall mean age was 10.64±3.199 years. Mean symptom score and clinical signs score gradually reduced on each follow-up (p<0.05). Mild recurrence was noted in 12(24%) patients who were managed with lubricants and anti-histamine topical drops. No complication was noted. CONCLUSIONS: Tacrolimus 0.1% was found to be effective and safe in the treatment of severe refractory vernal keratoconvinctivtis even when given once a day. Clinical Trial Registration: Chinese Clinical Trial Registry Id: ChiCTR2000031929 link: www.chictr.org.cn/hvshowproject.aspx?id=28053.

Treatment Patterns of Atopic Dermatitis Medication in 0-10-Year-Olds: A Nationwide Prescription-Based Study.

INTRODUCTION: The literature on treatment patterns for paediatric atopic dermatitis (AD) is scarce and is rarely based on real-world data. Using national registers, we sought to establish up-to-date, population-based prevalence estimates, predictors of risk and disease burden and a comprehensive overview of treatment patterns and course for paediatric patients with AD. METHODS: Dispensed prescriptions for the entire Norwegian child population aged 0-10 years from 2014 to 2020 were analysed. RESULTS: There were 176,458 paediatric patients with AD. Of these, 99.2% received topical corticosteroids, 5.1% received topical calcineurin inhibitors, 37.1% received potent topical corticosteroids and 2.1% received systemic corticosteroids. Of the 59,335 live births in Norway (2014), 14,385 [24.8%; 95% confidence interval (CI) 24.5-25.1] paediatric patients were treated for AD before the age of 6 years, and of these, only 934 (6.5%; 95% CI 6.1-6.9) received medication annually for 5 years or more. Compared with girls, 17.9% (95% CI 6.5-27.9) more boys were treated for at least 5 years, receiving 6.4% (95% CI 1.2-11.3) more potent topical corticosteroids and 12.4% (95% CI 6.5-18.0) more were treated for skin infections. Compared with patients with late-onset treatment, 18.9% (95% CI 7.5-29.0) more paediatric patients with early-onset treatment were still receiving treatment at 5 years of age, 15.7% (95% CI 7.1-23.4) more paediatric patients received potent topical corticosteroids and 44.4% (95% CI 36.5-51.2) more paediatric patients were treated for skin infections. CONCLUSION: Most paediatric patients were treated for a mild disease for a limited period. Although the prevalence of AD is higher at a younger age, these paediatric patients were the least likely to receive potent topical corticosteroids. Male sex and early-onset AD are associated with and are potential predictors of long-term treatment and treatment of potent topical corticosteroids, antihistamines and skin infections, which may have clinical utility for personalised prognosis, healthcare planning and future AD prevention trials.

Clinical management of psoriasis patients during the COVID-19 pandemic.

Psoriasis is a systemic immune-mediated inflammatory disease that requires consistent treatment and follow-up. Given that COVID-19 will persist in the coming years, dermatologists need to adjust their practices accordingly to care for their patients, particularly psoriasis patients managed with systemic therapies. We provide guidelines for optimizing care for psoriasis patients, including considerations for medication management, lifestyle adjustments, and utilization of telemedicine.

Anafilaxia ao ácido poli-L-láctico / Poly-L-lactic acid anaphylaxis

Paciente feminina, 47 anos, previamente hígida, apresentou reação anafilática associada ao uso do ácido poli-L-láctico (PLLA). Imediatamente após a administração do bioestimulador, a paciente referiu edema de face que evoluiu para urticária generalizada, edema em membros inferiores e tremores. Posteriormente, apresentou edema de língua e dificuldade para falar. Teste de puntura com extratos de PLLA na concentração pura 1:1 e testes intradérmicos na diluição 1:10 e 1:100 mostrou-se positivo. Paciente negou cofatores no dia do procedimento e alergias prévias. O presente artigo descreve o primeiro caso da literatura de anafilaxia ao PLLA, onde se discute aspectos da reação anafilática e exames usados para o diagnóstico.

A previously healthy 47-year-old woman had an anaphylactic reaction caused by poly-L-lactic acid (PLLA). Immediately after the administration of the biostimulating agent, the patient reported facial edema, which progressed to generalized urticaria, lower extremity edema, and tremors. Then she had tongue edema and difficulties to talk. A prick test with pure PLLA extracts (1:1) and intradermic tests (1:10 and 1:100 dilutions) were positive. The patient denied cofactors on procedure day as well as previous allergies. This is the first case report of anaphylaxis due to PLLA and includes a discussion of aspects of the anaphylactic reaction and tests that were used to provide the diagnosis.

Effectiveness of skin cleanser and protectant regimen on incontinence-associated dermatitis outcomes in acute care patients: A cluster randomised trial.

Skin cleansers and protectants protect skin from incontinent matter to reduce the risk of incontinence-associated dermatitis (IAD), but their effectiveness treating established IAD in the tropics is unknown. We conducted an open-label cluster randomised trial to compare the effectiveness of a combined regimen of (1) specialised skin cleansers with disposable body wipes and (2) either an acrylic terpolymer (T1) or zinc oxide (T2) skin protectant against disposable body wipes and zinc oxide protectant (control) in promoting IAD healing and reducing the risk of deterioration. Eighty-four patients were recruited in a tertiary hospital in Singapore between April 2019 and January 2020 (T1: n = 23; T2: n = 37; Control: n = 24). Although not statistically significant, patients treated with T1 and T2 were 1.5 times as likely to experience IAD healing within seven days compared with the control (P = .66). Healing was more pronounced in participants with skin loss treated with T1 or T2. No treatment was superior in preventing IAD deterioration, the prevalence of which remained small (8%-14%). While skin cleaning and protectants reduced the overall risk of skin deterioration, the addition of skin cleansers enhanced IAD healing within a short period, an important consideration for future research examining IAD treatment in acute care.

Occlusive treatment enhances efficacy of tacrolimus 0.1% in a pediatric patient with severe alopecia areata: Case report and literature review.

Tacrolimus is an immunomodulatory drug, available for topical and systemic treatment of several dermopathies that are characterized by immune dysregulation. In the case of alopecia areata, standard application has proven insufficient to yield satisfactory results. Herein, we present a 6-year-old patient with Down syndrome who was treated with topical tacrolimus 0.1% ointment under occlusion overnight with remarkable clinical improvement within 4 months.

Efficacy and safety of dupilumab in two adolescents with severe atopic dermatitis / Eficácia e segurança do uso de dupilumabe em dois adolescentes com dermatite atópica grave

ABSTRACT We report the cases of two adolescent siblings with severe atopic dermatitis, who, despite weighing approximately 40kg, presented a good response to dupilumab with the off-label dose for individuals aged 12 years and weighing 60kg. Both had already used cyclosporine, azathioprine, methotrexate and oral corticosteroids for long periods, plus topical treatments with no adequate disease control. Skin lesions were constant and widespread, with frequent skin infections and very poor quality of life, with numerous physical and psychosocial consequences, such as dropping out of school activities due to severe itching, appearance and bullying. They also showed delayed growth and development. In 2018, dupilumab, an immunobiological agent, was approved for treatment of moderate to severe atopic dermatitis in adults and, in 2019, extended to the 12-17-year age group. Although it had already been approved by the Brazilian Health Surveillance Agency, the 200mg presentation (indicated for the weight of patients) was not available, with no expected arrival date. Therefore, weighing the risks and benefits of the situation of both, we chose to treat them with an adult dose (loading dose of 600mg subcutaneously, and 300mg subcutaneously every 2 weeks) despite the low weight. So far, they have received eight injections, showing significant improvement of disease and quality of life. There were no major adverse effects, only worsening of allergic conjunctivitis in one of them. The patients and their family are very satisfied, and we believe that the therapy has been successful.

RESUMO Relatamos os casos de dois irmãos adolescentes com dermatite atópica grave e que, apesar de pesarem cerca de 40kg, apresentaram boa resposta ao dupilumabe com a dose off-label para indivíduos com 12 anos e peso de 60kg. Ambos já tinham usado ciclosporina, azatioprina, metotrexato e corticoide oral por longos períodos, acrescidos de tratamentos tópicos sem controle adequado da doença. As lesões cutâneas eram constantes e disseminadas, e os irmãos apresentavam infeções de pele frequentes e qualidade de vida muito ruim, com inúmeras consequências físicas e psicossociais, como o abandono da atividade escolar pelo prurido intenso, pela aparência e pelo bullying sofrido. Apresentavam também retardo de crescimento e de desenvolvimento. Em 2018, o dupilumabe, um agente imunobiológico, foi aprovado para o tratamento de dermatite atópica moderada a severa para adultos e, em 2019, ampliado para faixa etária de 12 a 17 anos. Embora já tivesse a aprovação da Agência Nacional de Vigilância Sanitária no Brasil, a apresentação de 200mg (indicada para o peso dos pacientes) não estava disponível, sem previsão de chegada. Assim, pesando os riscos e benefícios da situação de ambos, optamos por tratá-los com dose de adulto (ataque de 600mg por via subcutânea e 300mg por via subcutânea a cada 2 semanas) apesar do baixo peso. Até o momento, eles realizaram oito aplicações, apresentando importante melhora da doença e da qualidade de vida. Não houve efeitos adversos importantes - apenas a piora da conjuntivite alérgica em um deles. Os pacientes e sua família estão muito satisfeitos, e nós avaliamos que a terapia está sendo bem-sucedida.

Efficacy and Safety of Diclofenac + Capsaicin Gel in Patients with Acute Back/Neck Pain: A Multicenter Randomized Controlled Study.

INTRODUCTION: Back and neck pain are common musculoskeletal disorders. Topical non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used to reduce pain and inflammation with fewer systemic side effects and drug interactions compared with oral NSAIDs. This study assessed efficacy and tolerability of a topical combination of capsaicin + diclofenac to treat acute back/neck pain. METHODS: In a randomized, double-blind, controlled, multicenter, parallel group trial, 746 patients were treated twice-daily for 5 days with diclofenac 2% + capsaicin 0.075%, diclofenac 2%, capsaicin 0.075% or placebo. Efficacy assessments included change and area under the curve in pain on movement for the worst procedure (POMWP), change in pressure algometry, and number of patients with decrease in POMWP of ≥ 30% and ≥ 50%. Adverse events (AEs) were recorded. RESULTS: Change in POMWP between baseline and day 2 evening, 1 h after drug application, demonstrates superiority of the combination (- 3.05 cm) versus diclofenac alone (- 2.33 cm) and placebo (- 2.45 cm), but not capsaicin alone (- 3.26 cm). AEs were consistent with known safety profiles. CONCLUSION: Capsaicin alone and capsaicin + diclofenac showed superior benefit compared with placebo. However, diclofenac alone demonstrated efficacy comparable with placebo, and therefore its addition to capsaicin added no increased pain relief over capsaicin alone. TRIAL REGISTRATION: ClinicalTrials.gov identifier; NCT02700815.

Optimizing Communication About Topical Corticosteroids: A Quality Improvement Study [Formula: see text].

BACKGROUND: Patients are often non-adherent to topical corticosteroids (TCS). This may be in part due to poor communication between patients and dermatologists. OBJECTIVES: This quality improvement (QI) study aims to describe dermatologist-patient communication about TCS treatments and to compare communication before and after the implementation of an educational intervention. METHODS: This QI study assesses the communication between dermatologists and new dermatology outpatients receiving a TCS prescription in a tertiary care center. The QI intervention is 2-pronged, consisting of an educational pamphlet for patients and a communication workshop for the dermatology team. Encounters were audiotaped, and communication was analyzed using a coding system (MEDICODE). Phase 1 recordings happened preintervention and reflect the usual dermatologist-patient communication in this practice setting and phase 2 recordings were postintervention. RESULTS: Phase 1 reveals that dermatologists frequently address informational medication themes, such as naming the medications and informing patients about their proper use. They less frequently discuss patient experience themes, such as goals of treatment, adverse effects of treatments, and exploring patients' emotions about medications (such as anxiety, fears, etc.). After the intervention, there was more frequent discussion of patient experience themes without increasing consultation length. But, in both phases, physicians address most themes as a monolog with little verbal input from patients. CONCLUSIONS: Our study raises awareness regarding dermatologists' communication patterns about TCS, identifying specific areas for improvement, such as discussions of adverse effects, and explicitly addressing patients' attitudes and emotions. This is an essential step to foster a sense-making of TCS for patients.

A systematic review and meta-analysis of the efficacy and safety of the interleukin (IL)-12/23 and IL-17 inhibitors ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab and tildrakizumab for the treatment of moderate to severe plaque psoriasis.

OBJECTIVE: To systematically analyze the efficacy and safety of interleukin (IL)-12/23, IL-17, and selective IL-23 inhibitors in moderate to severe plaque psoriasis. METHODS AND RESULTS: Twenty-four randomized placebo-controlled trials were included. Compared to placebo, risk ratios (RR) of achieving PASI-75 and PGA/IGA 0/1 respectively were 20.20 (95% CI 13.82-29.54, p < .00001) and 14.55 (10.42-20.31, p < .00001) for ustekinumab 90 mg, 13.75 (8.49-22.28, p < .00001) and 9.81 (5.70-16.89, p < .00001) for ustekinumab 45 mg, 17.65 (12.38-25.17, p < .00001) and 26.13 (16.05-42.53, p < .00001) for secukinumab 300 mg, 15.36 (10.76-21.94, p < .00001) and 20.91 (12.82-34.13, p < .00001) for secukinumab 150 mg, 18.22 (10.63-31.23, p < .000001) and 18.82 (10.36-34.16, p < .00001) for ixekizumab 80 mg every 4 weeks, 19.83 (11.07-35.52, p < .00001) and 20.41 (11.01-37.81, p < .00001) for ixekizumab 80 mg every 2 weeks, 14.79 (9.86-22.16, p < .00001) and 21.93 (15.52-31.01, p < .00001) for brodalumab 210 mg, 11.55 (7.77-17.18, p < .00001) and 16.59 (11.72-23.49, p < .00001) for brodalumab 140 mg, 12.40 (8.87-17.34, p < .00001) and 10.84 (7.91-14.85, p < .00001) for guselkumab 100 mg, 11.45 (7.45-17.58, p < .00001) and 10.97 (6.44-18.69, p < .00001) for tildrakizumab 200 mg, 11.02 (7.17-16.93, p < .00001) and 10.03 (6.45-15.59, p < .00001) for tildrakizumab 100 mg. Similar outcomes were seen for PASI-90. Safety was satisfactory for each therapy at any dose, but a slightly increased risk of withdrawal due to toxicity was observed in individuals receiving ixekizumab compared to placebo. CONCLUSION: Ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab were highly efficacious and generally well-tolerated when used as treatments for moderate to severe plaque psoriasis.

Safety of a formulation containing chitosan microparticles with chamomile: blind controlled clinical trial / Segurança de uma formulação contendo micropartículas de quitosana com camomila: ensaio clínico, mascarado e controlado / Seguridad de una formulación conteniendo micropartículas de quitosano con manzanilla: ensayo clínico, enmascarado y controlado

ABSTRACT Objective: to evaluate the safety of a topical formulation containing chamomile microparticles coated with chitosan in the skin of healthy participants. Method: phase I blind, controlled, non-randomized, single-dose clinical trial with control for skin, base formulation, and formulation with microparticles. The variables analyzed were irritation and hydration by the Wilcoxon and Kruskall-Wallis tests. Results: the study started with 35 participants with a mean age of 26.3 years. Of these, 30 (85.71%) were female, 29 (82.90%) were white skinned and 32 (91.40%) had no previous pathologies. One participant was removed from the study reporting erythema at the site of application, and four other participants for not attending the last evaluation. In the 30 participants who completed the study, the tested formulation did not cause erythema, peeling, burning, pruritus or pain; there was an improvement in cutaneous hydration in the site of application of the formulation with microparticles. In the evaluation of the barrier function, there was an increase in transepidermal water loss in all sites. Conclusion: the formulation with chamomile microparticles is safe for topical use, not causing irritation and improving skin hydration over four weeks of use. Its effects on barrier function need further investigation. No. RBR-3h78kz in the Brazilian Registry of Clinical Trials (ReBEC).

RESUMO Objetivo: avaliar a segurança de uma formulação tópica, contendo micropartículas de camomila revestidas com quitosana, na pele de participantes saudáveis. Método: ensaio clínico fase I, mascarado, controlado, não aleatorizado, de dose única, com controles da pele, da base da formulação e da formulação com micropartículas. As variáveis analisadas foram irritação e hidratação por meio dos testes de Wilcoxon e Kruskall-Wallis. Resultados: iniciaram o estudo 35 participantes com idade média de 26,3 anos. Destes, 30 (85,71%) eram do sexo feminino, 29 (82,90%) brancos e 32 (91,40%) sem patologias prévias. Um participante foi descontinuado por referir eritema no local de aplicação e quatro por não comparecerem à última avaliação. Nos 30 participantes que finalizaram o estudo, a formulação teste não causou eritema, descamação, ardor, prurido ou dor; houve melhora na hidratação cutânea no local de aplicação da formulação com as micropartículas. Na avaliação da função barreira houve aumento da perda transepidérmica de água em todos os locais. Conclusão: a formulação com micropartículas de camomila é segura para o uso tópico, não provocando irritação e melhorando a hidratação cutânea ao longo de quatro semanas de uso. Seus efeitos na função barreira devem ser melhor estudados. N° RBR-3h78kz no Registro Brasileiro de Ensaios Clínicos (ReBEC).

RESUMEN Objetivo: evaluar la seguridad de una formulación tópica, conteniendo micropartículas de manzanilla revestidas con quitosano, en la piel de participantes sanos. Método: ensayo clínico fase I, enmascarado, controlado, no aleatorizado, de dosis única, con controles de la piel, de la base de la formulación y de la formulación con micropartículas. Las variables analizadas fueron irritación e hidratación por medio de los tests de Wilcoxon y Kruskall-Wallis. Resultados: iniciaron el estudio 35 participantes con edad media de 26,3 años. De esos, 30 (85,71%) eran del sexo femenino, 29 (82,90%) blancos y 32 (91,40%) sin patologías previas. Un participante fue descontinuado por referir eritema en el local de aplicación y cuatro por no comparecer a la última evaluación. En los 30 participantes que finalizaron el estudio, la formulación test no causó eritema, descamación, ardor, prurito o dolor; hubo mejora en la hidratación cutánea en el local de aplicación de la formulación con las micropartículas. En la evaluación de la función barrera hubo aumento de la pérdida transepidérmica de agua en todos los locales. Conclusión: la formulación con micropartículas de manzanilla es segura para el uso tópico, no provocando irritación y mejorando la hidratación cutánea a lo largo de cuatro semanas de uso. Sus efectos en la función barrera deben ser mejor estudiados. N° RBR-3h78kz en el Registro Brasilero de Ensayos Clínicos (ReBEC).

Current status and future prospects for biologic treatments of psoriasis.

INTRODUCTION: Biological agents have transformed psoriasis treatment by selectively targeting immune signaling molecules involved in psoriasis pathogenesis. While biologics offer the most effective treatment of moderate to severe psoriasis, they are not without complications. Some patients treated with biologics have poor clinical responses, form anti-drug antibodies, or develop adverse events. Additionally, there is growing need for head-to-head studies comparing biologic treatment regimens, efficacy, and safety. Areas covered: Here we review the literature surrounding biologics already in clinical use and those undergoing development and clinical trials. We also investigate the development and approval of small molecules inhibitors and biosimilars used to treat psoriasis. Expert commentary: As the psoriasis treatment armamentarium continues to expand, it is important to follow the safety profile of these drugs both in clinical trials and in post-marketing registries to ensure their long-term safety. Physicians must be aware of the limitations of existing safety data of a drug and the potential risk for rare adverse events when selecting appropriate treatments and monitoring patient outcomes.

Predictors of biologic treatment of psoriasis: a non-interventional study.

BACKGROUND: Biologic therapies represent a significant advance in the treatment of psoriasis. However, no studies have examined the patient characteristics predictive of biologic treatment of psoriasis. The purpose of this study was to ascertain the frequency and predictors of treatment of psoriasis with biologics in three European countries, ie, France, Spain, and the UK. METHODS: This was a cross-sectional analysis of physician-recorded demographic and clinical data on patients receiving either conventional or biologic treatments for psoriasis. Data were drawn from the Adelphi 2007 Psoriasis Disease Specific Program (DSP®), a multinational, real-world survey of patients with psoriasis consulting practicing dermatologists. The numbers of patients treated with biologic and nonbiologic agents were recorded. Data were subjected to bivariate analysis according to treatment regimen (biologic versus nonbiologic). Predictors of treatment with biologics were identified by logistic regression analysis. RESULTS: A total of 2,509 psoriasis patients were included in this study (1,374 from France, 561 from Spain, and 574 from the UK). Biologic use was most prevalent in Spain (19.4% of patients), followed by the UK (9.1%), and France (8.4%). In the logistic regression analysis, psoriatic arthritis was a statistically significant predictor of increased biologic use in France (odds ratio [OR] 5.38, 95% confidence interval [CI] 3.32-8.77), Spain (OR 2.71, 95% CI 1.16-6.33), and the UK (OR 8.70, 95% CI 3.65-20.83). Physician-assessed moderate-to-severe disease was also a statistically significant predictor of increased biologic use in France (OR 5.08, 95% CI 2.01-12.82), Spain (OR 11.11, 95% CI 4.33-28.57), and the UK (OR 8.55, 95% CI 1.11-66.67). CONCLUSION: In this study, an average of about one tenth of psoriasis patients enrolled in Spain, France, and the UK were treated with biologics in 2007. Physician-assessed moderate-to-severe disease and presence of psoriatic arthritis were significantly associated with biologic use in all three countries.

Alleged isotretinoin-associated inflammatory bowel disease: disproportionate reporting by attorneys to the Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Some studies have purported to link isotretinoin prescribed for acne with the development of inflammatory bowel disease (IBD). OBJECTIVE: We sought to identify existence of disproportionate attorney-initiated reporting of isotretinoin-associated IBD in the Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: A total of 3,338,835 cases (2003-2011) were downloaded from the FAERS. These were queried for IBD cases reported with isotretinoin for a usage indication of acne while recording reporter category. Trends were analyzed over time for reports by attorneys for all medications compared with reports of IBD with isotretinoin. Signal inflation factor was calculated to determine the distortion of pharmacovigilance signals for IBD with isotretinoin. RESULTS: There were 2214 cases of IBD resulting from isotretinoin. Attorneys reported 1944 (87.8%) cases whereas physicians reported 132 (6.0%) and consumers reported 112 (5.1%) cases (P value < .01). For the entire FAERS, only 87,905 of the total 2,451,314 (3.6%) reports for all drug reactions during the same time period were reported by attorneys (P value < .01). The signal inflation factor for IBD with isotretinoin for attorney-initiated reports was 5.82, signifying a clear distortion. LIMITATIONS: The accuracy of reports was not ascertained. CONCLUSIONS: Attorney-initiated reports inflate the pharmacovigilance signal of isotretinoin-associated IBD in the FAERS.

The effect of isotretinoin on triglycerides and liver aminotransferases / Influência da isotretinoína nas transaminases hepáticas e triglicerídeos

BACKGROUND: Isotretinoin has been used to treat the most severe cases of acne; however, it may provoke adverse events in mucocutaneous and hepatic tissues, lead to alterations in lipid levels and cause teratogenicity. OBJECTIVE: The objective of this study was to evaluate the profile of changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride levels in patients who had been treated with oral isotretinoin dispensed by the São Mateus/ES pharmacy for special drugs. METHODS: A retrospective, observational, longitudinal study was conducted by carrying out a secondary analysis of each patient's data. RESULTS: Of the 130 patients who received isotretinoin between January and December 2009, only 70 were actually treated for 3 months or more and handed in the results of their laboratory tests. Of these 70 patients, 39 (55.7%) were female. The mean age of the women (23.9 years) was higher than the mean age of the men (20.1 years). There was a statistically significant increase in the levels of triglycerides (87.01 ± 48.25 versus 105.32 ± 48.76 mg/dL), AST (20.44 ± 6.26 versus 24.38 ± 11.92 U/L) and ALT (18.24 ± 8.31 versus 23.34 ± 20.03 U/L) performed prior to and 3 months or more after oral isotretinoin treatment. After treatment with oral isotretinoin, triglyceride levels had increased beyond the normal range in 11% of the patients, while 8.6% had elevated AST levels and 7.3% had increased ALT levels. CONCLUSION: The results in this population show that the use of oral isotretinoin for the treatment of acne may result in altered triglyceride, AST and ALT levels. These findings are in accordance with data published previously in the scientific literature, confirming the need to monitor these patients.

FUNDAMENTOS: A isotretinoína tem sido usada no tratamento dos casos mais graves de acne, embora possa induzir reações adversas nos tecidos mucocutâneos e hepáticos, alterações nos níveis lipídicos e teratogenicidade. OBJETIVOS: Este estudo avaliou o perfil de alterações nas concentrações de Alanina Aminotransferrase, Aspartato Aminotransferrase e triglicerídeos em pacientes que fizeram uso de isotretinoína oral fornecida pelo serviço Farmácia de Medicamentos Excepcionais de São Mateus/ES. MÉTODOS: Foi realizado estudo observacional longitudinal exploratório retrospectivo, utilizando coleta de dados secundários de cada paciente. RESULTADOS: Dos 130 pacientes que receberam isotretinoína no período de janeiro a dezembro de 2009, somente 70 realizaram o tratamento por 3 meses ou mais e apresentaram os resultados dos exames. Desses 70 pacientes, 39 (55,7%) eram do sexo feminino. A média de idade das mulheres (23,9 anos) foi maior do que a média de idade dos homens (20,1 anos). Houve aumento estatisticamente significante nas dosagens de triglicerídeos (87,01±48,25 versus 105,32 ± 48,76), Aspartato Aminotransferrase (20,44 ± 6,26 versus 24,38 ± 11,92) e Alanina Aminotransferrase (18,24 ± 8,31 versus 23,34 ± 20,03), realizadas antes e após 3 meses ou mais de tratamento com isotretinoína oral. Após o tratamento com isotretinoína oral, 11% dos pacientes apresentaram elevação de triglicerídeos acima dos valores normais, 8,6% apresentaram elevação da Aspartato Aminotransferrase e 7,3% tiveram elevação da Alanina Aminotransferrase. CONCLUSÃO: Os resultados mostraram que o uso de isotretinoína oral para o tratamento da acne, na população estudada, pode levar a alterações nas dosagens de triglicerídeos, Alanina Aminotransferrase e Aspartato Aminotransferrase, como mostrado pela literatura científica, confirmando a necessidade de monitoramento.